Differential sensitivity to hypoxia enables shape-based classification of sickle cell disease and trait blood samples

Abstract

AbstractDifferentiating between homozygous (disease) and heterozygous (trait) sickle cell patients is the key to ensuring appropriate long-term disease management. Well-equipped labs needed to perform confirmatory diagnostic tests are not available in endemic areas of most low- and medium-income countries. As a consequence of hemoglobin polymerization, red blood cells (RBCs) become sickle shaped and stiff under hypoxic conditions in sickle cell anemia patients. A simple test such as microscopy, using RBC shape as a biophysical marker, cannot conclusively differentiate between homozygous (disease) and heterozygous (trait) sickle blood. Here, we establish a new paradigm of microscopic diagnosis of sickle cell disease by exploiting differential polymerization of hemoglobin in disease and trait RBCs under controlled, chemically-induced hypoxia in a microfluidic chip. We use a portable smartphone microscope to compare the RBC shape distributions in blood treated with high and low concentrations of the hypoxia-inducing agent to correctly identify 35 blood samples as healthy, sickle cell disease or trait. Finally, we demonstrate our test in remote field locations to enable fast and confirmed diagnosis of sickle cell anemia in resource-limited areas.